According to the MR method in general, the body of the patient to be examined is arranged in a strong, uniform magnetic field whose direction at the same time defines an axis (normally the z-axis) of the co-ordinate system on which the measurement is based. The magnetic field produces different energy levels for the individual nuclear spins in dependence on the magnetic field strength which can be excited (spin resonance) by application of an electromagnetic alternating field (RF field) of defined frequency (so-called Larmor frequency, or MR frequency). From a macroscopic point of view, the distribution of the individual nuclear spins produces an overall magnetization which can be deflected out of the state of equilibrium by application of an electromagnetic pulse of appropriate frequency (RF pulse) while the magnetic field of the RF pulse extends perpendicular to the z-axis, so that the magnetization performs a precession about the z-axis. This motion of the magnetization describes a surface of a cone whose angle of aperture is referred to as flip angle. The magnitude of the flip angle is dependent on the strength and the duration of the applied electromagnetic pulse. In the case of a so-called 90° pulse, the spins are deflected from the z axis to the transverse plane (flip angle 90°). The RF pulse is radiated toward the body of the patient via a RF coil arrangement of the MR device. The RF coil arrangement typically surrounds the examination volume in which the body of the patient is placed.
After termination of the RF pulse, the magnetization relaxes back to the original state of equilibrium, in which the magnetization in the z direction is built up again with a first time constant T1 (spin lattice or longitudinal relaxation time), and the magnetization in the direction perpendicular to the z direction relaxes with a second time constant T2 (spin-spin or transverse relaxation time). The variation of the magnetization can be detected by means of receiving RF coils which are arranged and oriented within the examination volume of the MR device in such a manner that the variation of the magnetization is measured in the direction perpendicular to the z-axis. The decay of the transverse magnetization is accompanied, after application of, for example, a 90° pulse, by a transition of the nuclear spins (induced by local magnetic field inhomogeneities) from an ordered state with the same phase to a state in which all phase angles are uniformly distributed (dephasing). The dephasing can be compensated by means of a refocusing pulse (for example a 180° pulse). This produces an echo signal (spin echo) in the receiving coils.
In order to realize spatial resolution in the body, linear magnetic field gradients extending along the three main axes are superposed on the uniform magnetic field, leading to a linear spatial dependency of the spin resonance frequency. The signal picked up in the receiving coils then contains components of different frequencies which can be associated with different locations in the body. The signal data obtained via the receiving coils corresponds to the spatial frequency domain and is called k-space data. The k-space data usually includes multiple lines acquired with different phase encoding. Each line is digitized by collecting a number of samples. A set of k-space data is converted to a MR image by means of Fourier transformation.
In some medical applications, the difference in MR signal intensity from standard MR protocols, i.e. the contrast, between different tissues might not be sufficient to obtain satisfactory clinical information. In this case, contrast enhancing techniques are applied, which rely for example on advanced MR sequences or on MR contrast agents, like paramagnetic agents (Gd-DTPA/DOTA), or combinations of both.
In a number of important MR applications with or without using contrast agents, advanced contrast enhancing MR techniques are favorable, which employ long and/or repeatedly applied preparation RF pulses, for example for saturation transfer, hetero- or homonuclear polarization transfer, proton decoupling or spin locking.
A particularly promising approach for contrast enhancement and increase of MR detection sensitivity (by orders of magnitude) is the known method based on ‘Chemical Exchange Saturation Transfer’ (CEST), as initially described by Balaban et al. (see e.g. U.S. Pat. No. 6,962,769 B1). With this CEST technique, the image contrast is obtained by altering the intensity of the water proton signal in the presence of a contrast agent with a fast-relaxing proton pool resonating at a slightly different frequency than the main water resonance. This is achieved by selectively saturating the nuclear magnetization of the pool of exchangeable protons which resonate at a frequency different from the water proton resonance. Exchangeable protons can be provided by exogenous CEST contrast agents (e.g. DIACEST, PARACEST or LIPOCEST agents), but can also be found in biological tissue (e.g. endogenous amide protons in proteins and peptides or protons in glucose, not covered in the original Balaban method). A frequency-selective preparation RF pulse that is matched to the MR frequency of the exchangeable protons is used for this purpose. The saturation of the MR signal of the exchangeable protons is subsequently transferred to the MR signal of nearby water protons within the body of the examined patient by chemical exchange or dipolar coupling with the water protons, thereby decreasing the water proton MR signal. The selective saturation at the MR frequency of the exchangeable protons thus gives rise to a negative contrast in a proton-density weighted MR image. Amide proton transfer (APT) MR imaging of endogenous exchangeable protons allows highly sensitive and specific detection of pathological processes on a molecular level, like increased protein concentrations in malignant tumor tissue. The APT signal is also sensitively reporting on locally altered pH levels—because the exchange rate is pH dependent—which can be e.g. used to characterize ischemic stroke. CEST contrast agents have several important advantages over T1- and T2-based MR contrast agents. CEST contrast agents allow for multiplexing by using a single compound or a mixture of compounds bearing exchangeable protons that can be addressed separately in a multi-frequency CEST MR examination. This is of particular interest for molecular imaging, where multiple biomarkers may be associated with several unique CEST frequencies. Moreover, the MR contrast in APT/CEST MR imaging can be turned on and off at will by means of the frequency selective preparation RF pulse. Adjustable contrast enhancement is highly advantageous in many applications, for example when the selective uptake of the contrast agent in the diseased tissue in examined body is slow.
A problem of all known APT/CEST MR imaging techniques is that the selective saturation prior to the actual acquisition of image data takes a comparably long time. The build-up of the saturation of the exchangeable protons is a relatively slow process (the characteristic timescale is on the order of one second). Consequently, the desirable saturation period for APT/CEST measurements is typically 2-5 seconds. Then, immediately following the saturation period, an imaging sequence including a (slice-selective) excitation RF pulse is usually applied for excitation of bulk water nuclear magnetization and one or more MR signals are recorded, for example as gradient echoes or spin echoes. The acquisition of individual MR signals used for imaging takes typically several milliseconds up to a few hundred milliseconds, wherein the full k-space is acquired as a set of these short signal acquisitions.
Further, in the paper ‘Magnetisation transfer contrast in MR imaging of the heart’ by R. S. Balaban et al. in Radiology 180(1991)671-675 a gated acquisition of magnetic resonance signals is mentioned for MTF transfer. Off-resonance irradiation is applied during interpulse delay.
In clinical applications for MR examination of body regions affected by motion (for example abdominal organs like liver, prostate, and kidneys), APT/CEST MR imaging should be combined with motion detection to acquire MR signals in a defined motion state. For example, MR imaging of abdominal organs is affected by respiratory motion. Hence, APT/CEST MR imaging should be combined with breathing triggering to acquire the MR signals in a defined respiratory phase (e.g. full expiration). Triggering the imaging sequence for MR signals acquisition by detected motion signals is per se known in the art. However, a conventional motion triggering, in which the imaging sequence is initiated upon the respective trigger signal, would be inappropriate and inefficient for APT/CEST MR imaging. The motion phase will have changed until the MR signal acquisition starts several seconds later, because, for example the human breathing interval, which amounts to 3-5 seconds, covers a time scale which is similar to the duration of the selective saturation prior to the actual MR signal acquisition. Furthermore, in the described example, waiting for the trigger signal indicating the desired respiratory phase will take up to one complete breathing cycle, which compromises scan efficiency.
Until today, no efficient combination of APT/CEST MR imaging with motion triggering has been described in the art.
From the foregoing it is readily appreciated that there is a need for an improved MR imaging technique. It is consequently an object of the invention to provide a MR imaging method and a MR device which enable high-quality MR imaging of moving body portions using APT/CEST.